Evidence for MHC restriction of soluble helper effects was observed in the generation of syngeneic killer T cells to TNP-altered self. Ia bearing T cells obscure the observation of such interactions, thus, must be removed in order to detect MHC restriction of "nonspecific" soluble helper factor supernatants. Genetic mapping studies demonstrated that the strain producing HFS must be compatible in the H-2IA, H-2IB region of the H-2 MHC with the strain utilizing the helper molecules in order for optimal helper signals to be delivered.